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Review
. 2019 Jan 27;24(3):451.
doi: 10.3390/molecules24030451.

Metabolism and Biological Activities of 4-Methyl-Sterols

Sylvain Darnet  1 , Hubert Schaller  2
Affiliations
Review

Metabolism and Biological Activities of 4-Methyl-Sterols

Sylvain Darnet et al. Molecules. .

Abstract

4,4-Dimethylsterols and 4-methylsterols are sterol biosynthetic intermediates (C4-SBIs) acting as precursors of cholesterol, ergosterol, and phytosterols. Their accumulation caused by genetic lesions or biochemical inhibition causes severe cellular and developmental phenotypes in all organisms. Functional evidence supports their role as meiosis activators or as signaling molecules in mammals or plants. Oxygenated C4-SBIs like 4-carboxysterols act in major biological processes like auxin signaling in plants and immune system development in mammals. It is the purpose of this article to point out important milestones and significant advances in the understanding of the biogenesis and biological activities of C4-SBIs.

Keywords: 4-methylsterol; C4-demethylation complex (C4DMC); development; genetic disease; hormone; steroid; sterol.

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Conflict of interest statement

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Figures

Figure 1
Figure 1
Sterol and 4-methylsterol structures. (A) carbon numbering. (B) some compounds described in this article. (C) dinosterol and a sterane, a biogeological marker.
Figure 2
Figure 2
C4-demethylation pathways in mammals and fungi, and plants. Sterol nomenclature is given in Table 1. (A) pathways in mammals and fungi; (B) pathway in plants; C4-demethylation in eukaryotes: SMO, sterol-4α-methyl-oxidase; C4D, 3β-hydroxysteroid dehydrogenases/C-4 decarboxylase; SKR, sterone ketoreductase, C14-demethylation: CYP51, lanosterol-C14 demethylase. SMT, sterol methyltransferase; 14R, sterol-14-reductase. Each arrow represents an enzymatic step. Graphical insets are from references ([24] in top and [25] bottom panels).
Figure 3
Figure 3
Dafachronic acid synthesis in Caenorhabditis elegans. Sterol nomenclature is given in Table 1. C4-demethylation in eukaryotes: HSD-1, 3-hydroxysteroid dehydrogenase/Δ5/Δ4 isomerase (HSD-1); STRM-1, Sterol 4-C-methyltransferase; DAF-9, steroid cytochrome P450 hydroxylase; DAF-36, cholesterol 7-desaturase. Each arrow represents an enzymatic step.
Figure 4
Figure 4
Sterol pathways in Methylococcus capsulatus. Sterol nomenclature is given in Table 1. CYP51, lanosterol-C14 demethylase; 14R, sterol-14-reductase; Sdm, sterol demethylase. Each arrow represents an enzymatic step.
Figure 5
Figure 5
Chemical inhibitors for C4-SBI accumulation.
See this image and copyright information in PMC

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